Major Depressive Disorder; Symptoms, Diagnosis, Treatment

Major Depressive Disorder; Symptoms, Diagnosis, Treatment

Major depressive disorder also known as unipolar or major depression is characterized by a persistent feeling of sadness or a lack of interest in outside stimuli. It is a mental disorder characterized by at least two weeks of low mood that is present across most situations. It is often accompanied by low self-esteem, loss of interest in normally enjoyable activities, low energy, and pain without a clear cause. People may also occasionally have false beliefs or see or hear things that others cannot. Some people have periods of depression separated by years in which they are normal while others nearly always have symptoms present. Major depressive disorder can negatively affect a person’s personal, work, or school life, as well as sleeping, eating habits, and general health. Between 2–7% of adults with major depression die by suicide, and up to 60% of people who die by suicide had depression or another mood disorder.

Subtypes of Major Depressive Disorder

The DSM-IV-TR recognizes five further subtypes of MDD, called specifiers, in addition to noting the length, severity and presence of psychotic features:

  • Melancholic depression –  is characterized by a loss of pleasure in most or all activities, a failure of reactivity to pleasurable stimuli, a quality of depressed mood more pronounced than that of grief or loss, a worsening of symptoms in the morning hours, early-morning waking, psychomotor retardation, excessive weight loss (not to be confused with anorexia nervosa), or excessive guilt.
  • Atypical depression – is characterized by mood reactivity (paradoxical anhedonia) and positivity, significant weight gain or increased appetite (comfort eating), excessive sleep or sleepiness (hypersomnia), a sensation of heaviness in limbs known as leaden paralysis, and significant social impairment as a consequence of hypersensitivity to perceived interpersonal rejection.
  • Catatonic depression – is a rare and severe form of major depression involving disturbances of motor behavior and other symptoms. Here, the person is mute and almost stuporous, and either remains immobile or exhibits purposeless or even bizarre movements. Catatonic symptoms also occur in schizophrenia or in manic episodes or may be caused by the neuroleptic malignant syndrome.
  • Postpartum depression –  or mental and behavioral disorders associated with the puerperium, not elsewhere classified, refers to the intense, sustained and sometimes disabling depression experienced by women after giving birth. Postpartum depression has an incidence rate of 10–15% among new mothers. The DSM-IV mandates that, in order to qualify as postpartum depression, onset occur within one month of delivery. It has been said that postpartum depression can last as long as three months.
  • Persistent depressive disorder (also called dysthymia) is a depressed mood that lasts for at least two years. A person diagnosed with a persistent depressive disorder may have episodes of major depression along with periods of less severe symptoms, but symptoms must last for two years to be considered a persistent depressive disorder.
  • Seasonal affective disorder (SAD) –  is a form of depression in which depressive episodes come on in the autumn or winter, and resolve in spring. The diagnosis is made if at least two episodes have occurred in colder months with none at other times, over a two-year period or longer.
  • Psychotic depression –  often develops if you have been hallucinating or you believe in delusions that are not cohesive with reality. This can be caused by a traumatic event or if you have already had a form of depression in the past.
  • Postpartum depression – is a common occurrence among new mothers experiencing hormonal changes following childbirth. The stress of raising a new child and changes in and to your body can greatly affect your mood. Additionally, the Canadian Mental Health Association states that parents who adopt can also suffer some of the symptoms of postpartum depression.

Causes of Major Depressive Disorder

It’s not known exactly what causes depression. As with many mental disorders, a variety of factors may be involved, such as:

  • Biological differences – People with depression appear to have physical changes in their brains. The significance of these changes is still uncertain, but may eventually help pinpoint causes.
  • Brain chemistry – Neurotransmitters are naturally occurring brain chemicals that likely play a role in depression. Recent research indicates that changes in the function and effect of these neurotransmitters and how they interact with neurocircuits involved in maintaining mood stability may play a significant role in depression and its treatment.
  • Hormones – Changes in the body’s balance of hormones may be involved in causing or triggering depression. Hormone changes can result with pregnancy and during the weeks or months after delivery (postpartum) and from thyroid problems, menopause or a number of other conditions.
  • Inherited traits – Depression is more common in people whose blood relatives also have this condition. Researchers are trying to find genes that may be involved in causing depression.
  • Personality/temperamental factors (predisposing toward depression) – neuroticism, rumination, stress vulnerability, impulsivity, negative cognitive style.
  • Personality/temperamental factors (protective against depression) – openness, trust, acceptance, stress coping.
  • External factors – early life events, provoking life events, seasonal changes, social support.
  • Internal factors – hormones, biological rhythm generators, comorbid disorders

Symptoms of Major Depressive Disorder

Treatment of Major Depressive Disorder

Primary care providers often start treatment for MDD by prescribing antidepressant medications.

Selective serotonin reuptake inhibitors (SSRIs)

These antidepressants are frequently prescribed. SSRIs work by helping inhibit the breakdown of serotonin in the brain, resulting in higher amounts of this neurotransmitter.

Serotonin is a brain chemical that’s believed to be responsible for mood. It may help improve mood and produce healthy sleeping patterns. People with MDD often have low levels of serotonin. An SSRI can relieve symptoms of MDD by increasing the amount of available serotonin in the brain.

SSRIs include well-known drugs such as fluoxetine  and citalopram . They have a relatively low incidence of side effects that most people tolerate well.

Other medications of Major Depressive Disorder

Tricyclic antidepressants and medications known as atypical antidepressants may be used when other drugs haven’t helped. They can cause several side effects, including weight gain and sleepiness.

Note: Some medications used to treat MDD aren’t safe for women who are pregnant or breastfeeding. Make sure you speak with your healthcare provider if you become pregnant, you’re planning to become pregnant, or you’re breastfeeding your child.


Psychotherapy, also known as psychological therapy or talk therapy, can be an effective treatment for people with MDD. It involves meeting with a therapist on a regular basis to talk about your condition and related issues. Psychotherapy can help you:

  • adjust to a crisis or other stressful event
  • replace negative beliefs and behaviors with positive, healthy ones
  • improve your communication skills
  • find better ways to cope with challenges and solve problems
  • increase your self-esteem
  • regain a sense of satisfaction and control in your life

Electroconvulsive Therapy (ECT) 

It is a medical treatment most commonly used for patients with severe major depression or bipolar disorder who have not responded to other treatments. It involves a brief electrical stimulation of the brain while the patient is under anesthesia. A patient typically receives ECT two to three times a week for a total of six to 12 treatments. ECT has been used since the 1940s, and many years of research have led to major improvements. It is usually managed by a team of trained medical professionals including a psychiatrist, an anesthesiologist and a nurse or physician assistant.

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Brain Stimulation Therapies for Major Depressive Disorder

If medications do not reduce the symptoms of depression, electroconvulsive therapy (ECT) may be an option to explore. Based on the latest research:

  • Major Depressive Disorder
  • Electroconvulsive therapy can be an effective treatment for depression. In some severe cases where a rapid response is necessary or medications cannot be used safely, ECT can even be a first-line intervention.
  • Once strictly an inpatient procedure, today ECT is often performed on an outpatient basis. The treatment consists of a series of sessions, typically three times a week, for two to four weeks.
  • ECT may cause some side effects, including confusion, disorientation, and memory loss. Usually these side effects are short-term, but sometimes memory problems can linger, especially for the months around the time of the treatment course. Advances in ECT devices and methods have made modern ECT safe and effective for the vast majority of patients. Talk to your doctor and make sure you understand the potential benefits and risks of the treatment before giving your informed consent to undergoing ECT.
  • ECT is not painful, and you cannot feel the electrical impulses. Before ECT begins, a patient is put under brief anesthesia and given a muscle relaxant. Within one hour after the treatment session, which takes only a few minutes, the patient is awake and alert.

Lifestyle changes for Major Depressive Disorder

In addition to taking medications and participating in therapy, you can help improve MDD symptoms by making some changes to your daily habits.

  • Eating right – Consider eating foods that contain omega-3 fatty acids, such as salmon. Foods that are rich in B vitamins, such as beans and whole grains, have also been shown to help some people with MDD. Magnesium has also been linked to fighting MDD symptoms. It’s found in nuts, seeds, and yogurt.
  • Avoiding alcohol and certain processed foods – It’s beneficial to avoid alcohol, as it’s a nervous system depressant that can make your symptoms worse. Also, certain refined, processed, and deep-fried foods contain omega-6 fatty acids, which may contribute to MDD.
  • Getting plenty of exercises – Although MDD can make you feel very tired, it’s important to be physically active. Exercising, especially outdoors and in moderate sunlight, can boost your mood and make you feel better.
  • Sleeping well – It’s vital to get at least 6 to 8 hours of sleep per night. Talk to your doctor if you’re having trouble sleeping.

Beyond Treatment: Things You Can Do for Major Depressive Disorder

Here are other tips that may help you or a loved one during treatment for depression:

  • Try to be active and exercise.
  • Set realistic goals for yourself.
  • Try to spend time with other people and confide in a trusted friend or relative.
  • Try not to isolate yourself, and let others help you.
  • Expect your mood to improve gradually, not immediately.
  • Postpone important decisions, such as getting married or divorced, or changing jobs until you feel better. Discuss decisions with others who know you well and have a more objective view of your situation.
  • Continue to educate yourself about depression.

Summary Of Practice Guideline For The Treatment Of Patients With Major Depressive Disorder. 3rd ed. – American Psychiatric Association (2010)

Rating Scheme for the Strength of the Recommendations

Each recommendation is identified as falling into one of three categories of endorsement, indicated by a bracketed Roman numeral following the statement. The three categories represent varying levels of clinical confidence:

  • increase your self-esteem
  • Recommended with substantial clinical confidence.
  • Recommended with moderate clinical confidence.
  • May be recommended on the basis of individual circumstances.

Major Recommendations for Major Depressive Disorder

Provide Education to the Patient and the Family

  • With the patient’s permission, family members and others involved in the patient’s day-to-day life may also benefit from education about the illness, its effects on functioning (including family and other interpersonal relationships), and its treatment
  • Common misperceptions about antidepressants (e.g., they are addictive) should be clarified.
  • In addition, education about major depressive disorder should address the need for a full acute course of treatment, the risk of relapse, the early recognition of recurrent symptoms, and the need to seek treatment as early as possible to reduce the risk of complications or a full-blown episode of major depression
  • Patients should also be told about the need to taper antidepressants, rather than discontinuing them precipitously, to minimize the risk of withdrawal symptoms or symptom recurrence.
  • Patient education also includes general promotion of healthy behaviors such as exercise, good sleep hygiene, good nutrition, and decreased use of tobacco, alcohol, and other potentially deleterious substances.
  • Educational tools such as books, pamphlets, and trusted websites can augment the face-to-face education provided by the clinician [I].

Treatment Of Acute Phase Of Major Depressive Disorder


  • increase your self-esteem
  • An antidepressant medication is recommended as an initial treatment choice for patients with mild to moderate major depressive disorder [I] and definitely should be provided for those with severe major depressive disorder unless ECT is planned.
  • Because the effectiveness of antidepressant medications is generally comparable between classes and within classes of medications, the initial selection of an antidepressant medication will largely be based on the anticipated side effects, and additional factors such as medication response in prior episodes, cost, and patient preference.
  • For most patients, a selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI), mirtazapine, or bupropion is optimal.
  • In general, the use of nonselective monoamine oxidase inhibitors (MAOIs) (e.g., phenelzine, tranylcypromine, isocarboxazid) should be restricted to patients who do not respond to other treatments [I], given the necessity for dietary restrictions with these medications and the potential for deleterious drug-drug interactions.
  • In patients who prefer complementary and alternative therapies, S-adenosyl methionine (SAMe) [III] or St. John’s wort [III] might be considered, although evidence for their efficacy is modest at best.

Careful attention to drug-drug interactions is needed with St. John’s Wort

  • Patients receiving pharmacotherapy should be systematically monitored on a regular basis to assess their response to treatment and assess patient safety.
  • If antidepressant side effects do occur, an initial strategy is to lower the dose of the antidepressant or to change to an antidepressant that is not associated with that side effect.

Other Somatic Therapies

  • ECT is recommended as a treatment of choice for patients with severe major depressive disorder that is not responsive to psychotherapeutic and/or pharmacological interventions, particularly in those who have significant functional impairment or have not responded to numerous medication trials .
  • ECT is also recommended for individuals with major depressive disorder who have associated psychotic or catatonic features [I], for those with an urgent need for response (e.g., patients who are suicidal or nutritionally compromised due to refusal of food or fluids) , and for those who prefer ECT or have had a previous positive response to ECT .
  • Bright light therapy might be used to treat seasonal affective disorder as well as nonseasonal depression .

Psychotherapy for Major Depressive Disorder

  • Use of a depression-focused psychotherapy alone is recommended as an initial treatment choice for patients with mild to moderate major depressive disorder , with clinical evidence supporting the use of cognitive-behavioral therapy (CBT) , interpersonal psychotherapy , psychodynamic therapy , and problem-solving therapy  in individual and in group formats.
  • In women who are pregnant, wish to become pregnant, or are breastfeeding, a depression-focused psychotherapy alone is recommended  and depending on the severity of symptoms, should be considered as an initial option .
  • As with patients who are receiving pharmacotherapy, patients receiving psychotherapy should be carefully and systematically monitored on a regular basis to assess their response to treatment and assess patient safety .
  • Marital and family problems are common in the course of major depressive disorder, and such problems should be identified and addressed, using marital or family therapy when indicated .
  • The combination of psychotherapy and antidepressant medication may be used as an initial treatment for patients with moderate to severe major depressive disorder .
  • Combining psychotherapy and medication may be a useful initial treatment even in milder cases for patients with psychosocial or interpersonal problems, intrapsychic conflict, or co-occurring personality disorder .

Assessing the Adequacy of Treatment Response

  • Onset of benefit from psychotherapy tends to be a bit more gradual than that from medication, but no treatment should continue unmodified if there has been no symptomatic improvement after 1 month .
  • Generally, 4-8 weeks of treatment are needed before concluding that a patient is partially responsive or unresponsive to a specific intervention .

Strategies to Address Nonresponse

  • For individuals who have not responded fully to treatment, the acute phase of treatment should not be concluded prematurely, as an incomplete response to treatment is often associated with poor functional outcomes.
  • If at least a moderate improvement in symptoms is not observed within 4-8 weeks of treatment initiation, the diagnosis should be reappraised, side effects assessed, complicating co-occurring conditions and psychosocial factors reviewed, and the treatment plan adjusted. It is also important to assess the quality of the therapeutic alliance and treatment adherence.
  • For patients in psychotherapy, additional factors to be assessed include the frequency of sessions and whether the specific approach to psychotherapy is adequately addressing the patient’s needs.
  • With some TCAs, a drug blood level can help determine if additional dose adjustments are required.
  • For patients treated with an antidepressant, optimizing the medication dose is a reasonable first step if the side effect burden is tolerable and the upper limit of a medication dose has not been reached.
  • Particularly for those who have shown minimal improvement or experienced significant medication side effects, other options include augmenting the antidepressant with a depression-focused psychotherapy or with other agents or changing to another non-MAOI antidepressant.
  • Patients may be changed to an antidepressant from the same pharmacological class (e.g., from one SSRI to another SSRI) or to one from a different class (e.g., from an SSRI to a tricyclic antidepressant.
  • For patients who have not responded to trials of SSRIs, a trial of an SNRI may be helpful.
  • Augmentation of antidepressant medications can utilize another non-MAOI antidepressant, generally from a different pharmacological class, or a non-antidepressant medication such as lithium thyroid hormone, or a second-generation antipsychotic
  • Additional strategies with less evidence for efficacy include augmentation using anticonvulsant, omega-3 fatty acids, folate, or a psychostimulant medication, including modafinil.
  • If anxiety or insomnia are prominent features, consideration can be given to anxiolytic and sedative-hypnotic medications, including buspirone, benzodiazepines, and selective gamma-aminobutyric acid (GABA) agonist hypnotics (e.g., zolpidem, eszopiclone).
  • For patients whose symptoms have not responded adequately to medication, ECT remains the most effective form of therapy and should be considered .
  • In patients capable of adhering to dietary and medication restrictions, an additional option is changing to a nonselective MAOI  after allowing sufficient time between medications to avoid deleterious interactions .
  • Transdermal selegiline, a relatively selective MAO B inhibitor with fewer dietary and medication restrictions, or transcranial magnetic stimulation could also be considered .
  • Vagus nerve stimulation (VNS) may be an additional option for individuals who have not responded to at least four adequate trials of antidepressant treatment, including ECT .
  • For patients treated with psychotherapy, consideration should be given to increasing the intensity of treatment or changing the type of therapy . If psychotherapy is used alone, the possible need for medications in addition to or in lieu of psychotherapy should be assessed .
  • Patients who have a history of poor treatment adherence or incomplete response to adequate trials of single treatment modalities may benefit from combined treatment with medication and a depression-focused psychotherapy [II].
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Treatment Of Continuation Phase Of Major Depressive Disorder

During the continuation phase of treatment, the patient should be carefully monitored for signs of possible relapse.

  • Systematic assessment of symptoms, side effects, adherence, and functional status is essential and may be facilitated through the use of clinician- and/or patient-administered rating scales.
  • To reduce the risk of relapse, patients who have been treated successfully with antidepressant medications in the acute phase should continue treatment with these agents for a 4-9 month.
  • In general, the dose used in the acute phase should be used in the continuation phase
  • To prevent a relapse of depression in the continuation phase, depression-focused psychotherapy is recommended, with the best evidence available for cognitive-behavioral therapy.
  • Patients who respond to an acute course of ECT should receive continuation pharmacotherapy, with the best evidence available for the combination of lithium and nortriptyline. Alternatively, patients who have responded to an acute course of ECT may be given continuation ECT, particularly if medication or psychotherapy has been ineffective in maintaining remission.

Treatment Of Maintenance Phase Of Major Depressive Disorder

In order to reduce the risk of a recurrent depressive episode, patients who have had three or more prior major depressive episodes or who have chronic major depressive disorder should proceed to the maintenance phase of treatment after completing the continuation phase

  • Maintenance therapy should also be considered for patients with additional risk factors for recurrence, such as the presence of residual symptoms, ongoing psychosocial stressors, early age at onset, and family history of mood disorders
  • For many patients, particularly for those with chronic and recurrent major depressive disorder or co-occurring medical and/or psychiatric disorders, some form of maintenance treatment will be required indefinitely.
  • During the maintenance phase, an antidepressant medication that produced symptom remission during the acute phase and maintained remission during the continuation phase should be continued at a full therapeutic dose.
  • If a depression-focused psychotherapy has been used during the acute and continuation phases of treatment, maintenance treatment should be considered, with a reduced frequency of sessions.
  • For patients whose depressive episodes have not previously responded to acute or continuation treatment with medications or a depression-focused psychotherapy but who have shown a response to ECT, maintenance ECT may be considered.
  • Maintenance treatment with vagus nerve stimulation is also appropriate for individuals whose symptoms have responded to this treatment modality.

Due to the risk of recurrence, patients should be monitored systematically and at regular intervals during the maintenance phase . Use of standardized measurement aids is recommended for the early detection of recurrent symptoms .

Discontinuation of Treatment

When pharmacotherapy is being discontinued, it is best to taper the medication over the course of at least several weeks .

To minimize the likelihood of discontinuation symptoms, patients should be advised not to stop medications abruptly and to take medications with them when they travel or are away from home.

  • A slow taper or temporary change to a longer half-life antidepressant (e.g., fluoxetine) may reduce the risk of discontinuation syndrome  when discontinuing antidepressants or reducing antidepressant doses.
  • Before the discontinuation of active treatment, patients should be informed of the potential for a depressive relapse and a plan should be established for seeking treatment in the event of recurrent symptoms .
  • After discontinuation of medications, patients should continue to be monitored over the next several months and should receive another course of adequate acute phase treatment if symptoms recur .
  • For patients receiving psychotherapy, it is important to raise the issue of treatment discontinuation well in advance of the final session, although the exact process by which this occurs will vary with the type of therapy.

Clinical Factors Influencing Treatment for Major Depressive Disorder

Psychiatric Factors

Factors to consider in determining the nature and intensity of treatment include (but are not limited to) the nature of the doctor-patient alliance, the availability and adequacy of social supports, access to and lethality of suicide means, the presence of a co-occurring substance use disorder, and past and family history of suicidal behavior.

For suicidal patients, psychiatrists should consider an increased intensity of treatment, including hospitalization when warranted and/or combined treatment with pharmacotherapy and psychotherapy.

For patients who exhibit psychotic symptoms during an episode of major depressive disorder, treatment should include a combination of antipsychotic and antidepressant medications or ECT .

  • When patients exhibit cognitive dysfunction during a major depressive episode, they may have an increased likelihood of future dementia, making it important to assess cognition in a systematic fashion over the course of treatment.
  • Catatonic features that occur as part of a major depressive episode should be treated with a benzodiazepine or barbiturate typically in conjunction with an antidepressant. If catatonic symptoms persist, ECT is recommended. To reduce the likelihood of general medical complications, patients with catatonia may also require supportive medical interventions, such as hydration, nutritional support, prophylaxis against deep vein thrombosis, turning to reduce risks of decubitus ulcers, and passive range of motion to reduce the risk of contractures. If antipsychotic medication is needed, it is important to monitor for signs of the neuroleptic malignant syndrome, to which patients with catatonia may have a heightened sensitivity.
  • Benzodiazepines may be used adjunctively in individuals with major depressive disorder and co-occurring anxiety although these agents do not treat depressive symptoms, and careful selection and monitoring is needed in individuals with co-occurring substance use disorders.

In patients who smoke, bupropion or nortriptyline may be options to simultaneously treat depression and assist with smoking cessation.

  • When possible, a period of substance abstinence can help determine whether the depressive episode is related to substance intoxication or withdrawal [II]. Factors that suggest a need for antidepressant treatment soon after cessation of substance use include a family history of major depressive disorder and a history of major depressive disorder preceding the onset of the substance use disorder or during periods of sobriety.
  • For patients who have a personality disorder as well as major depressive disorder, psychiatrists should institute treatment for the major depressive disorder and consider treatment for personality disorder symptoms
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Demographic and Psychosocial Factors

When prescribing medications to women who are taking oral contraceptives, the potential effects of drug-drug interactions must be considered

For women in the perimenopausal period, SSRI and SNRI antidepressants are useful in ameliorating depression as well as in reducing somatic symptoms such as hot flashes.

  • Both men and women who are taking antidepressants should be asked whether sexual side effects are occurring with these medications . Men for whom trazodone is prescribed should be warned of the risk of priapism
  • For women who are currently receiving treatment for depression, a pregnancy should be planned, whenever possible, in consultation with the treating psychiatrist, who may wish to consult with a specialist in perinatal psychiatry
  • In women who are pregnant, planning to become pregnant, or breastfeeding, depression-focused psychotherapy alone is recommended and should always be considered as an initial option, particularly for mild to moderate depression, for patients who prefer psychotherapy, or for those with a prior positive response to psychotherapy
  • Antidepressant medication should be considered for pregnant women who have moderate to the severe major depressive disorder as well as for those who are in remission from a major depressive disorder, are receiving maintenance medication, and are deemed to be at high risk for a recurrence if the medication is discontinued
  • When antidepressants are prescribed to a pregnant woman, changes in pharmacokinetics during pregnancy may require adjustments in medication doses
  • Electroconvulsive therapy may be considered for the treatment of depression during pregnancy in patients who have psychotic or catatonic features, whose symptoms are severe or have not responded to medications, or who prefer treatment with ECT
  • When a woman decides to nurse, the potential benefits of antidepressant medications for the mother should be balanced against the potential risks to the newborn from receiving antidepressant in the mother’s milk.
  • For women who are depressed during the postpartum period, it is important to evaluate for the presence of suicidal ideas, homicidal ideas, and psychotic symptoms. The evaluation should also assess parenting skills for the newborn and for other children in the patient’s care
  • In individuals with late-life depression, identification of co-occurring general medical conditions is essential, as these disorders may mimic depression or affect choice or dosing of medications. Older individuals may also be particularly sensitive to medication side effects (e.g., hypotension, anticholinergic effects) and require adjustment of medication doses for hepatic or renal dysfunction  In other respects, treatment for depression should parallel that used in younger age groups
  • When antidepressants are prescribed, the psychiatrist should recognize that ethnic groups may differ in their metabolism and response to medications
  • A family history of bipolar disorder or acute psychosis suggests a need for increased attention to possible signs of bipolar illness in the patient (e.g., with antidepressant treatment)
  • A family history of recurrent major depressive disorder increases the likelihood of recurrent episodes in the patient and supports a need for maintenance treatment
  • The family history of a response to a particular antidepressant may sometimes help in choosing a specific antidepressant for the patient
  • Because problems within the family may become an ongoing stressor that hampers the patient’s response to treatment, and because depression in a family is a major stress in itself, such factors should be identified and strong consideration given to educating the family about the nature of the illness, enlisting the family’s support, and providing family therapy, when indicated .
  • For patients who have experienced a recent bereavement, psychotherapy or antidepressant treatment should be used when the reaction to a loss is particularly prolonged or accompanied by significant psychopathology and functional impairment
  • Support groups may be helpful for some bereaved individuals.

Co-occurring General Medical Conditions

Communication with other clinicians who are providing treatment for general medical conditions is recommended

  • The clinical assessment should include identifying any potential interactions between medications used to treat depression and those used to treat general medical conditions.
  • Assessment of pain is also important as it can contribute to and co-occur with depression. In addition, the psychiatrist should consider the effects of prescribed psychotropic medications on the patient’s general medical conditions, as well as the effects of interventions for such disorders on the patient’s psychiatric condition.
  • In patients with preexisting hypertension or cardiac conditions, treatment with specific antidepressant agents may suggest a need for monitoring of vital signs or cardiac rhythm (e.g., electrocardiogram [ECG] with TCA treatment; heart rate and blood pressure assessment with SNRIs and TCAs).
  • When using antidepressant medications with anticholinergic side effects, it is important to consider the potential for increases in heart rate in individuals with cardiac disease, worsening cognition in individuals with dementia, development of bladder outlet obstruction in men with prostatic hypertrophy, and precipitation or worsening of narrow-angle glaucoma.
  • Some antidepressant drugs (e.g., bupropion, clomipramine, maprotiline) reduce the seizure threshold and should be used with caution in individuals with preexisting seizure disorders.
  • In individuals with Parkinson’s disease, the choice of an antidepressant should consider that serotonergic agents may worsen symptoms of the disease, that bupropion has potential dopamine agonist effects (benefitting symptoms of Parkinson’s disease but potentially worsening psychosis) , and that selegiline has antiparkinsonian and antidepressant effects but may interact with L-dopa and with other antidepressant agents
  • In treating the depressive syndrome that commonly occurs following a stroke, consideration should be given to the potential for interactions between antidepressants and anticoagulating (including antiplatelet) medications.
  • Given the health risks associated with obesity and the tendency of some antidepressant medications to contribute to weight gain, longitudinal monitoring of weight (either by direct measurement or patient report) is recommended, as well as the calculation of body mass index (BMI). If significant increases are noted in the patient’s weight or BMI, the clinician and patient should discuss potential approaches to weight control such as diet, exercise, change in medication, nutrition consultation, or collaboration with the patient’s primary care physician.
  • In patients who have undergone bariatric surgery to treat obesity, adjustment of medication formulations or doses may be required because of altered medication absorption
  • For diabetic patients, it is useful to collaborate with the patient’s primary care physician in monitoring diabetic control when initiating antidepressant therapy or making significant dosing adjustments.
  • Clinicians should be alert to the possibility of sleep apnea in patients with depression, particularly those who present with daytime sleepiness, fatigue, or treatment-resistant symptoms. In patients with known sleep apnea, treatment choice should consider the sedative side effects of medication, with minimally sedating options chosen whenever possible.
  • Given the significant numbers of individuals with unrecognized human immunodeficiency virus (HIV) infection and the availability of effective treatment, consideration should be given to HIV risk assessment and screening. For patients with HIV infection who are receiving antiretroviral therapy, the potential for drug-drug interactions needs to be assessed before initiating any psychotropic medications. Patients who are being treated with antiretroviral medications should be cautioned about drug-drug interactions with St. John’s wort that can reduce the effectiveness of HIV treatments.
  • In patients with hepatitis C infection, interferon can exacerbate depressive symptoms, making it important to monitor patients carefully for worsening depressive symptoms during the course of interferon treatment.
  • Because tamoxifen requires active 2D6 enzyme function to be clinically efficacious, patients who receive tamoxifen for breast cancer or other indications should generally be treated with an antidepressant (e.g., citalopram, escitalopram, venlafaxine, desvenlafaxine) that has minimal effect on metabolism through the cytochrome P450 2D6 isoenzyme.
  • When depression occurs in the context of chronic pain, SNRIs and TCAs may be preferable to other antidepressive agents.
  • When ECT is used to treat major depressive disorder in an individual with a co-occurring general medical condition, the evaluation should identify conditions that could require modifications in ECT technique (e.g., cardiac conditions, hypertension, central nervous system lesions) ; these should be addressed insofar as possible and discussed with the patient as part of the informed consent process .


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